A study led by the Duke Clinical Research Institute finds that high costs and multiple appeals to insurers are preventing access to PCSK9 inhibitors, a new class of drugs that lowers LDL cholesterol. This file image provided by Amgen Inc. shows the cholesterol-lowering drug Repatha, which is a PCSK9 inhibitor. Robert DawsonAP

A study led by the Duke Clinical Research Institute finds that high costs and multiple appeals to insurers are preventing access to PCSK9 inhibitors, a new class of drugs that lowers LDL cholesterol. This file image provided by Amgen Inc. shows the cholesterol-lowering drug Repatha, which is a PCSK9 inhibitor. Robert DawsonAP

These cholesterol drugs could be game-changers. But most can’t afford to pay

Most prescriptions for a class of drugs heralded as game-changers for people with stubbornly high cholesterol are going unfilled because of high out-of-pocket costs and challenges by pharmacy benefit managers, according to a study from the Duke Clinical Research Institute.

Two factors limited access: lack of insurance approval for the prescription and high copays. Fewer than half of patients prescribed a PCSK9 inhibitor ever received approval for the drug by their insurer.

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Even after approval, one in three patients failed to fill their prescription. Sticker shock was a key factor. A quarter of patients had copays over $300 per month for therapies that cost about $14,000 a year.

The net result was that just 31 percent of patients who were initially prescribed a PCSK9 inhibitor ever actually received the therapy, the researchers found.

“This study basically reveals a system of rationing by roadblocks,” said lead author Ann Marie Navar, M.D., Ph.D., assistant professor of medicine at the Duke Clinical Research Institute. “Access comes down to patients whose doctors are persistent enough to win payer approval through multiple appeals, and patients who can afford the out-of-pocket costs.”

This study basically reveals a system of rationing by roadblocks.

Ann Marie Navar, lead author of study

In their study, which was funded by a manufacturer of one of the drugs, Navar and colleagues analyzed a large database of pharmacy claims that included more than 45,000 prescriptions for PCSK9 inhibitors. These drugs work by blocking a protein in the liver called proprotein convertase subtilisin kexin 9 (PCSK9), setting off a chain of events that breaks down LDL cholesterol, the “bad cholesterol” that causes heart disease.

The drugs include evolocumab (brand name Repatha, manufactured by the study’s funder, Amgen, Inc.) and alirocumab (brand name Praluent). Both therapies were approved by the FDA in 2015 for people with familial hyperlipidemia (a form of very high cholesterol that runs in families) and those with established heart disease who have high cholesterol despite traditional statin therapy.

In the first year after the drugs’ approvals, the researchers found that nearly 80 percent of doctors’ prescriptions were rejected by pharmacy benefit managers that govern drug coverage for health insurance plans. Most of the requests (73.5 percent) were resubmitted, but only 47.2 percent eventually won approval.

The median time between initial submission and approval was about four days, but some patients waited nearly three months for therapy.

Among patients who received approval, about 35 percent never picked up the medication, which was almost entirely due to high out-of-pocket costs. For example, more than 90 percent of approved patients who had no copayment filled their prescription, but if the copayment was over $300, only about 20 percent filled the prescription.

“Copay alone was highly predictive of whether a patient would fill their prescription — even adjusting for patient demographics, pharmacy, payer and other factors,” said senior author Eric D. Peterson, M.D., executive director of the Duke Clinical Research Institute. “This leads to rationing of these new medications, often in the absence of alternative therapies. Those who cannot afford these high co-pays are left untreated.”

Navar said the study had a limitation, in that it was not designed to assess what was driving pharmacy benefit managers to reject requests for prescriptions. Most patients in the study had Medicare coverage, but it was unclear whether and what clinical factors were taken into account by different pharmacy benefit managers.

“The current system we have is at best a very blunt instrument to restrict use of high-cost therapies to those who need it most,” Peterson said. “We need to figure out a better way to contain costs. We also need to better identify which patients are the best candidates for prescribed therapies, so we can apply the same approval criteria across the board.”

Navar and Peterson receive funding from Amgen and other pharmaceutical manufacturers; full disclosures are provided in the published study.